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Trimming FAST Score 0.2 Points Improves NASH Over 72 Weeks
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EASL International Liver Congress, June 23-26, 2021
Mark Mascolini
Whittling the FibroScan-aspartate aminotransferase (FAST) score by 0.2 point improved nonalcoholic steatohepatitis (NASH) by several measures through 72 weeks, including resolution of NASH without worsening fibrosis and improvement in fibrosis without worsening NASH [1]. This 161-person analysis in Hong Kong found 72-week improvements in body weight, AST to platelet ratio index (APRI), and fibrosis measured by FIB-4.
Despite its dire impact on prognosis, NASH still has no therapies. Clinicians are also challenged in monitoring NASH because repeated liver biopsy is not feasible. Reliable noninvasive monitoring tests would be a boon, noted researchers from the Chinese University of Hong Kong who conducted this study. The FAST score combines the FibroScan liver stiffness measure (LSM) and controlled attenuation parameter (CAP) with the standard liver biomarker, aspartate aminotransferase (AST).
The analysis involved adults with biopsy-confirmed NASH enrolled in a phase 2 placebo-controlled trial of subcutaneous semaglutide for NASH, which found more NASH resolution without worsening fibrosis in the semaglutide arms [2]. Researchers randomized participants to once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or to placebo.
At EASL the investigators presented a post hoc analysis comparing changes in FAST score from baseline through week 72. The full analysis set included 320 people with a median age in the mid-50s, about 60% of them women. A subset analysis included 161 people who had a FAST score at baseline and week 72. They were similar in age and proportion of women to the full data set. Body mass index averaged above 35 kg/m2, well above the 30-kg/m2 obesity threshold, in the full data set and the subset analysis.
By week 52 in the subset analysis, people randomized to 0.2 mg or 0.4 mg of semaglutide had significantly greater drops in FAST score compared with placebo. Those significant differences held true through 72 weeks. People randomized to 0.1 mg of semaglutide had greater declines in FAST score than people randomized to placebo at weeks 52 and 72, but those differences did not reach statistical significance.
From baseline to week 72, statistical analysis linked improved FAST score (versus worsening FAST score) to three measures of histologic improvement in the 0.4-mg semaglutide arm and the placebo arm: (1) resolution of NASH without worsening fibrosis (mean change in FAST score -0.47, P = 0.008, with 0.4-mg semaglutide and -0.37, P = 0.016, with placebo), (2) improvement in fibrosis without worsening NASH (mean change in FAST -0.41, P = 0.016, with 0.4-mg semaglutide and -0.18, P = 0.126, with placebo), and (3) improvement in NASH activity score (mean change in FAST -0.39, P = 0.005, with 0.4-mg semaglutide and -0.25, P = 0.006, with placebo).
The researchers also linked improved FAST score (versus worsening score) to three individual components of NASH activity score in people randomized to 0.4 mg semaglutide or placebo: (1) improvement in steatosis (mean change in FAST score -0.43, P = 0.018, with 0.4 mg semaglutide and -0.40, P = 0.001, with placebo), (2) improvement in ballooning (mean change in FAST -0.43, P = 0.002 with 0.4 mg semaglutide and -0.21, P = 0.004, with placebo), and (3) improvement in lobular inflammation (mean change in FAST -0.39, P = 0.017, with 0.4 mg semaglutide and -0.23, P = 0.050, with placebo).
From baseline to week 72, lower FAST score was also associated with improvement in NASH activity score of 1 point or more and improvement in NASH activity score of 2 points or more.
A 0.2-point drop in FAST score correlated with four NASH improvements in all four study arms: (1) resolution of NASH without worsening fibrosis (sensitivity and specificity for 0.4 mg semaglutide 0.895 and 0.444), (2) improvement in fibrosis without worsening NASH (sensitivity and specificity for 0.4 mg semaglutide 0.769 and 0.200), (3) improvement in NASH activity score of 1 point or more (sensitivity and specificity for 0.4 mg semaglutide 0.821 and 1.000), and (4) improvement in NASH activity score of 2 points or more (sensitivity and specificity for 0.4 mg semaglutide 0.905 and 0.500).
Lower FAST score also correlated with improvements in other markers at week 72 in the 0.4-mg semaglutide and placebo arms, including body weight, APRI, FIB-4, and ALT.
The researchers concluded that "reduction in FAST score is associated with histological improvement in NASH activity."
References
1. Wong VWS, Anstee Q, Geerts A, et al. Change in FibroScan-aspartate aminotransferase (FAST) score is associated with histological improvement in non-alcoholic steatohepatitis activity. EASL International Liver Congress, June 23-26, 2021. Abstract OS-1556.
2. Newsome PN, Buchholtz K, Cusi K, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-1124. doi: 10.1056/NEJMoa2028395.
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